The present disclosure contemplates that, before non-invasive neuroimaging methods were widely available, knowledge about normal brain development was difficult to obtain as the classical approach, neuroanatomical observation, was limited by the low mortality of normal children. Following the introduction of computed tomography (CT) and positron emission tomography (PET), attempts to describe brain development were made. However, these techniques typically expose the subject to ionizing radiation. After the introduction of magnetic resonance imaging (MRI), normal brain development could be assessed in a more systematic fashion. MRI may provide excellent soft tissue contrast, may be repeatable, and/or has become more widely available. Consequently, normal brain development has been the focus of a growing number of MRI studies.
The present disclosure contemplates that functional brain imaging studies using functional magnetic resonance imaging (fMRI) have become common in adults and have extended to studies of normal functional brain development in children. The reduced risks associated with MRI scanning may make it feasible to use this modality to study normal brain development in healthy children and/or to examine children longitudinally using various neurocognitive stimulation paradigms. Although functional MRI may provide a powerful tool for imaging of brain functional development in children in various neurocognitive domains, with a few notable exceptions, published studies using fMRI to map normal brain development in children have examined relatively small numbers of children in non-representative age and demographic samples. For example, in a recent review of PubMed articles published in the past five years, 92% of 210 functional neuroimaging articles involving children involved adolescents 18 years or older and 98% involved sample sizes less than 15 per group. Non-representative samples, small sample sizes, variable magnet field strength, and/or non-standard methodologies utilized in these clinically motivated studies may make it difficult to generalize findings. Thus, larger-scale studies may be useful in order to make more reliable interpretations of pediatric fMRI data.
The present disclosure contemplates that functional neuroimaging with MRI at 3 Tesla may have now reached a level of technical maturity sufficient to warrant standardization of methodologies for use of this technology in large-scale, multi-site studies of normative brain development in children. Furthermore, normative reference data documenting age dependent changes in cerebral perfusion and BOLD effect may provide a fundamental building block for future studies of functional neuropathology in children using functional magnetic resonance imaging methods because abnormalities in the neural substrates of attention, language, memory, and/or other developing neurocognitive domains may be better understood against the backdrop of normal age-dependent trends in these same neural circuits. Consequently, further research regarding brain functional pathology may be set in the context of normal development of the neural circuitry supporting the corresponding neurocognitive domains. For example, the pattern of brain activity supporting sentential language processing in a 7 year old boy may look very different from that of an 18 year old girl, even in absence of language pathology or brain injury.